Abstract
Although embolization therapy has demonstrated success in impeding tumor growth, concerns persist regarding potential tumor recurrence and inadvertent embolization of non-target tissues. In this study, drawing inspiration from the natural targeting and coagulation process of platelets in injured blood vessels, platelets are engineered by integrating acid-sensitive, morphology-transformable nanoparticles onto their surface through supramolecular conjugation (PLT-NP). The nanoparticles are constructed through the self-assembly of a β-amyloid derived peptide (FFVLK) terminally functionalized with Fmoc, hexahistidine (His(6)), and a polyethylene glycol (PEG)-functionalized cyclodextrin (CD). The supramolecularly engineered platelets actively accumulate in the tumor tissue upon inducing a tumor blood vessel injury through tumor resection. In response to the local acidic microenvironment, the nanoparticles undergo a morphological transformation into nanofibers via spontaneous assembly of FFLVK into fibril structures through hydrogen bonding and β-sheet interactions, to artificially enhance the coagulation and aggregation of platelets, causing occlusion of tumor blood vessels. The supramolecularly engineered platelets efficiently embolize tumor blood vessels in a specific manner, effectively suppressing tumor growth, metastasis, and recurrence, thus offering a promising paradigm for combating cancer.